Pentaxins (or pentraxins) [(PUBMED:6356809), (PUBMED:7772283)] are a family of proteins which show, under electron microscopy, a discoid arrangement of five noncovalently bound subunits. Proteins of the pentaxin family are involved in acute immunological responses [(PUBMED:7772283)]. Three of the principal members of the pentaxin family are serum proteins: namely, C-reactive protein (CRP) [(PUBMED:9614930)], serum amyloid P component protein (SAP) [(PUBMED:9514915)], and female protein (FP) [(PUBMED:9583999)].

CRP is expressed during acute phase response to tissue injury or inflammation in mammals. The protein resembles antibody and performs several functions associated with host defence: it promotes agglutination, bacterial capsular swelling and phagocytosis, and activates the classical complement pathway through its calcium-dependent binding to phosphocholine. CRPs have also been sequenced in an invertebrate, Limulus polyphemus (Atlantic horseshoe crab), where they are a normal constituent of the hemolymph.

SAP is a vertebrate protein that is a precursor of amyloid component P. It is found in all types of amyloid deposits, in glomerular basement menbrane and in elastic fibres in blood vessels. SAP binds to various lipoprotein ligands in a calcium-dependent manner, and it has been suggested that, in mammals, this may have important implications in atherosclerosis and amyloidosis.

FP is a SAP homologue found in Mesocricetus auratus (Golden hamster). The concentration of this plasma protein is altered by sex steroids and stimuli that elicit an acute phase response.

Pentaxin proteins expressed in the nervous system are neural pentaxin I (NPI) and II (NPII) [(PUBMED:8884281)]. NPI and NPII are homologous and can exist within one species. It is suggested that both proteins mediate the uptake of synaptic macromolecules and play a role in synaptic plasticity. Apexin, a sperm acrosomal protein, is a homologue of NPII found in Cavia porcellus (Guinea pig) [(PUBMED:7798266)].

PTX3 (or TSG-14) protein is a cytokine-induced protein that is homologous to CRPs and SAPs, but its function is not yet known.

Using a new method for construction and database searches of sequence consensus strings, we have identified a new superfamily of protein modules comprising laminin G, thrombospondin N and the pentraxin families. The conserved patterns correspond mainly to hydrophobic core residues located in central beta strands of the known three-dimensional structures of two pentraxins, the human C-reactive protein and the serum amyloid P-component. Thus, we predict a similar jellyroll fold for all members of this superfamily. In addition, the conservation of two exposed aspartate residues in the majority of superfamily members suggests hitherto unrecognised functional sites.

Long pentraxins: an emerging group of proteins with diverse functions.

Cytokine Growth Factor Rev. 1996; 7: 191-202

Display abstract

The earliest described pentraxins, C reactive protein (CRP) and serum amyloid P component (SAP), are cytokine-inducible acute phase proteins implicated in innate immunity whose concentrations in the blood increase dramatically upon infection or trauma. The highly conserved family of pentraxins was thought to consist solely of approximately 25 kDa proteins. Recently, several distinct larger proteins have been identified in which only the C-terminal halves show characteristic features of the pentraxin family. One of the recently described "long" pentraxins (TSG-14/PTX3) is inducible by TNF or IL-1 and is produced during the acute phase response. Other newly identified long pentraxins are constitutively expressed proteins associated with sperm-egg fusion (apexin/p50), may function at the neuronal synapse (neuronal pentraxin I, NPI), or may serve yet other, unknown functions (NPII and XL-PXN1). Evidence obtained by molecular modeling and by direct physicochemical analysis suggests that TSG-14 protein retains some characteristic structural features of the pentraxins, including the formation of pentameric complexes.

BACKGROUND: Pentraxins are a family of plasma proteins characterized by their pentameric assembly and calcium-dependent ligand binding. The recent determination of the crystal structure for a member of this family, human serum amyloid P component (SAP), provides a basis for the comparative analysis of the pentraxin family. RESULTS: We have compared the sequences, tertiary structures and quaternary arrangements of SAP with human C-reactive protein (CRP), Syrian hamster SAP (HSAP) and Limulus polyphemus CRP (LIM). These proteins can adopt a beta-jelly roll topology and a hydrophobic core similar to that seen in SAP. Only minor differences are observed in the positions of residues involved in coordinating calcium ions. CONCLUSIONS: Calcium-mediated ligand binding by CRP, HSAP and LIM is similar to that defined by the crystal structure of SAP, but sequence differences in the hydrophobic pocket explain the differential ligand specificities exhibited by the homologous proteins. Differences elsewhere, including insertions and deletions, account for the different (hexameric) quaternary structure of LIM.